There is no admission that the background art disclosed in this section legally constitutes prior art.
In 2008, it is expected that 20,180 women will be diagnosed with ovarian cancer and 15,310 will succumb to the disease [1]. Ovarian cancer is a devastating illness in which only 20% of patients are diagnosed with stage I disease [2]. The poor prognosis associated with ovarian cancer is multi-factorial; a lack of minimally invasive, early detection tests, subtle symptom development and tumor chemo-resistance. Even with the advent of chemo-resistance assays it is still difficult to predict drug resistance and only 10-15% of patients will remain in prolonged remission after initial cytotoxic therapy.
While annual pelvic examination is widely practiced, it lacks the sensitivity to be used a screening strategy for ovarian cancer [3]. Women at high risk for ovarian cancer may typically undergo screening with trans-vaginal ultrasound and serum CA-125. CA-125, however, remains a poor marker for early stage disease with a documented sensitivity of 40% [4,5]. Additionally, it has been shown that even in a high-risk, screened population, incident cases are still more likely to be advanced stage [6]. The identification of biomarkers that may assist in treatment planning and prediction of chemotherapy outcomes is highly desirable in this population of patients.
There is emerging research about the role of microRNAs in a variety of pathologic conditions; including both solid and hematologic malignancies. MicroRNAs (miRNAs) are small, 22-25 nucleotide non-coding sequences of RNA. These sequences control gene expression either by translational repression or degradation of the messenger RNA transcript after targeting the 3′UTR. Early studies with Caenorhabditis elegans showed that a great number of these sequences are highly conserved across all species, demonstrating the important roles that miRNAs play in cellular differentiation, proliferation and cell cycle control [7]. It is now recognized that miRNAs are frequently de-regulated in malignancy. Under-expressed miRNAs such as let-7 in lung cancer and mirs-15/16 in leukemia, are tumor suppressor genes, suppressing Ras and BCL2 respectively [8,9]. Over-expressed miRNAs such as mir-21 and the cluster miR-17-92, are oncogenes (oncomirs), targeting tumor suppressors PTEN and E2F1 in solid and hematologic malignancies respectively [10,11]. While miRNA research in gynecologic malignancies is in its infancy, the miRNA signature profile of ovarian cancer has recently been published [12-14].
The diagnostic and prognostic utility of circulating RNAs in both benign and malignant conditions has recently been revealed. Placental-associated circulating miRNAs correlate with pregnancy progression [15]. In malignant states, circulating mRNAs in renal cell carcinoma patients [16], as well as miRNAs from the serum of patients with diffuse large B cell lymphoma [17], have been shown to be stable and highly predictive of malignancy as well as survival. Recently, it has been demonstrated that the miRNA signature of circulating tumor exosomes of ovarian cancer patients demonstrates high correlation with miRNA expression of the primary tumor [18]. Ovarian cancer remains a disease for which improved non-invasive, serum screening tests are highly desirable.
In spite of considerable research into therapies to treat these diseases, they remain difficult to diagnose and treat effectively, and the mortality observed in patients indicates that improvements are needed in the diagnosis, treatment and prevention of ovarian cancer.